New Anti-malignancy Drugs Promising And Offer Different Ways To Fight Cancer

August 25, 1985|Newhouse News Service

HMBA is a cancer drug with a radical difference, the forerunner of what some researchers envision as an entirely new family of anti-malignancy medications. Rather than kill cancer cells, it changes their biological behavior.

"Cancer is, in some ways, the failure of a cell to mature and develop into an adult version of that cell," says Dr. David A. VanEcho of the University of Maryland Cancer Center in Baltimore.

But in laboratory and animal tests, HMBA somehow stops the uncontrolled reproduction of cancer cells and allows them to mature and assume their normal functions.

The drug is one of a number of innovative treatments cancer researchers now are testing in humans as they seek new therapies to augment the established anti-cancer arsenal of surgery, radiation and toxic chemotherapy.

Among them:

- The biological response modifiers, natural substances and drugs that stimulate the body's natural defenses against cancer or change the behavior of cancer cells so they revert to normal. Interferon is the best known of the BRMs, but they also include HMBA and the aptly named tumor necrosis factor.

- Photodynamic therapy, the use of drugs that enter tumor cells but only kill them after they are exposed to light. "What is unique about this is that there is no known biological activity unless light is shined on it," says Dr. Richard L. Edelson of Columbia-Presbyterian Medical Center in New York.

Biological response modifiers are of particular interest, because they take advantage of the body's own biology to fight cancer. Thus, they are expected to have less severe side effects than the powerful anti-cancer drugs now in use that kill healthy as well as malignant cells.

But one certainty emerging from the early work with BRMs is that none is going to wipe out all cancers.

"There is not going to be a single 'magic bullet,' " says Dr. John R. Durant of the Fox Chase Cancer Center in Philadelphia. "There are going to be a lot of magic bullets. What we have to do is determine how to use them."

Interferon is the best studied of the BRMs, and the results have been mixed. There are actually three major types of interferon - alpha, beta and gamma, each with several subtypes.

Only alpha interferon has been tested widely in humans. Researchers have reported it appears effective against two rare leukemias, hairy celland chronic myelogenous. But the interferon appears more to retard the cancer's growth, rather than cure it.

Dr. Jorge R. Quesada of M.D. Anderson Hospital and Tumor Institute in Houston reported at a scientific meeting in May that 22 of 28 hairy cell patients responded to alpha interferon. At the same meeting, a report of a five-center study revealed 48 of 64 patients responded to it.

"Based on our experience, continuous treatment with alpha interferon may, in time, result in complete or partial remissions in the majority of these patients," Quesada told the American Society of Clinical Oncology.

Unfortunately, alpha interferon hasn't proved much use against more common killers, such as colon, breast, lung and liver cancers. Some evidence suggests that beta interferon might fight kidney cancer, but studies of beta and gamma aren't far enough along to adequately assess their success or failure.

"Interferon will probably find its way into the clinic, most likely in combination with established therapies," says Dr. Carl Pinsky of the federal National Cancer Institute.

Interleukin-2 is another natural chemical intriguing cancer researchers. It is a growth factor produced by T-cells - key players in the body's immune- system reaction to infections and cancers - that causes a rapid increase in T-cells.

Animal tests suggest removing T-cells, treating them with interleukin-2 and returning them to the body may at least reduce the size of a tumor and prevent its spread. The chemical is now in early testing in humans, both against cancer and acquired immune deficiency syndrome.

An even more exotic substance is tumor necrosis factor, produced by immune-system cells called macrophages. It was discovered in 1975 and found to kill mouse cancer cells without harming surrounding tissue.

More recently, animal studies have indicatedthat the factor is effective against a wide range of tumor cells, particularly when used with the interferons. Dr. Sydney E. Salmon of the University of Arizona College of Medicine in Tucson has reported a combination of TNF and gamma interferon killed 96 percent of myeloma cancer cells growing in a laboratory dish.

Last spring, Japanese researchers began giving TNF to 100 patients in an effort to determine its safety. U.S. doctors hope to begin their human tests before year's end.

TNC is a cancer-cell killer; HMBA may be a cancer-cell savior.

The drug, hexamethylene bisacetamide, seems to work by somehow putting a cancer cell back on its normal path of development.

HMBA's first human tests are now under way independently at two Baltimore medical schools, the University of Maryland and Johns Hopkins University, to check its safety and maximum dosage.

"So far most of the toxicity is minor," says VanEcho, who is conducting the University of Maryland trial with Dr. Merrill Egorin.

If HMBA or similar drugs prove out in cancer patients, VanEcho envisions them eventually being used to prevent cancer in people at high risk of developing certain malignancies.